Investigation of kisspeptin level in primary tumor and metastasis in the mouse breast cancer model with radiofrequency exposure

Cancer is a complex disease arising from various genetic and cellular changes. Breast cancer, the most common cancer worldwide, is a malignant type known for its high potential to metastasize to the lungs and liver. Breast cancer is categorized into subtypes based on microscopic appearance, biological behavior, and molecular and genetic information derived from tumor cells. Notably, among these subtypes, the triple-negative breast cancer stands out for its lack of targeted treatment options and elevated metastatic potential, drawing attention from researchers. Studies have indicated a potential connection between breast cancer and various environmental factors, such as radiofrequency exposure (3 kHz–300 GHz). Therefore, the investigation of the effects of radiofrequency fields, to which most individuals, particularly cancer patients, are inevitably exposed, has gained significant importance in recent years. Metastasis plays a crucial role in controlling and treating cancer. Kisspeptin, a product of the metastasis-suppressing gene KISS1, is believed to inhibit the formation and growth of tumors settled in metastatic regions. The uncertainty regarding the levels of kisspeptin in primary tumors and metastases following radiofrequency exposure persists and is intended to be explored in our study for the first time. In our research, an experimental breast cancer model was established using 4T1 breast cancer cell lines and BALB/c mice. The subjects were exposed to 900 MHz radiofrequency for 4 hours daily over a period of 7 days. At the conclusion of the applications, the subjects' breast/primary tumor, lung, and liver tissues were extracted. The observation indicated that radiofrequency application reduced kisspeptin levels in primary tumors and metastatic tissues of breast cancer subjects. Furthermore, the impacts on metastasis were evaluated through E-cadherin and VEGF expressions. Caspase-3 expression and the percentage of TUNEL-positive cells were examined to determine apoptosis, revealing an increase in apoptotic markers. This increase suggests that metastatic mechanisms might utilize apoptotic pathways as an escape route to sustain the viability of tumor cells. Keywords: Breast Cancer, Kisspeptin, Radiofrequency, Metastasis, Apoptosis